Reactivity of contact ion pairs in a charged monotopic receptor

An integrated FT-ICR and computational approach has been employed to investigate the gas phase structure and reactivity of ESI-formed complexes between organic and inorganic acids (HX) and a K+-containing hexaazamacrocycle (M). Two limiting structures are available to those complexes, either the classical [MK+·XH] or the zwitterionic [MH+·K+·X−] one, with the latter prevailing over the first by increasing the gas-phase acidity of the HX ligand. Both structures undergo the HX displacement when reacting with 2,4-pentanedione (P0) and its 1,1,1-trifluoro (P3) and 1,1,1,5,5,5-hexafluoro (P6) derivatives. The HX displacement efficiency is found to depend not only on the specific structure of the complex, but also on the acid/base properties of the diones. Among them, P3 displays the lowest reactivity towards the [MK+·XH] complexes. These findings are consistent with the co-existence of a direct HA-to-HX and a base-catalyzed A−-to-HX substitution channels. The P0 < P3 < P6 reactivity order, observed towards the zwitterionic [MH+·K+·X−] complexes, points to a HX displacement mechanism whose rate-determining step involves the prototropic transfer from HA to the X−moiety in the encounter complex. The present study provides an extremely rare piece of information on reactive events taking place on contact ion pairs (K+X−) inside a monotopic receptor (MH+).